: The ability to detect, and the preference for, sweet-tasting compounds presumably arose in humans and other animal to insure an adequate intake of calories and other nutrients. However, excess consumption of sweet substances has been implicated in a number of health disorders. Sweet-tasting substances are uniquely pleasant but the mechanisms by which they are detected and preferred remain unclear although much progress has been made in recent years. The investigator proposes use of behavioral, electrophysiological and molecular genetic techniques to further understanding of sweet taste perception. The ultimate goal is to locate and identify genes that influence the behavioral responses to sweet tasting compounds. This will be accomplished by study of two inbred strains of mice that differ substantially in their preference for many sweet-tasting components and in the physiological responses of their anterior taste nerve to sucrose. The observation that 2 genes on chromosome 4 contribute the strain difference will be further investigated. Four interrelated research activities are proposed. First, the difference between strains in a wide range of sweet and non-sweet compounds will be determined. Second, mice of the second filial generation will be bred, phenotyped and genotyped to isolate genetic regions responsible for the strain difference in behavioral responses to sweeteners. Third, congenic strains, differing only in a major locus influencing sweet taste will be produced as a prelude to identifying the gene(s) of interest. Finally, the behavioral and physiological mechanisms underlying gene function (in sweet taste perception) will be examined in more detail. This work will set the stage to positionally clone one or more genes that are involved in sweet taste perception.